Illustrious trio Barcelona, Liverpool and Bayern Munich, European champions 12 times between them, are all in danger of an early exit from the competition this week.
Holders Barcelona face former striker Samuel Eto'o in their tie against Inter where defeat, combined with a win for Russia's Rubin Kazan over Dynamo Kiev, would see them go out.
Five-times champions Liverpool have a relatively straightforward match away to table-propping Hungarians Debrecen but their fate is largely out of their hands as they will be eliminated if Fiorentina beat already-qualified Olympique Lyon at home.
Similarly, Bayern Munich host pointless Maccabi Haifa knowing that, even if they win as expected, they will go out if Juventus overcome a Girondins Bordeaux side who are also through to the last 16.
In other games, Arsenal should join Lyon, Bordeaux, Chelsea, Porto, Manchester United and Sevilla in the last 16 while Milan and Real Madrid also have good chances of making sure of their places.
Inter's visit to Barcelona tonight in Group F provides the highlight of the week.
The Italians top the group with six points after their last-gasp win in Dynamo Kiev two weeks ago, one ahead of Rubin Kazan and Barcelona with the Ukrainians a further point behind.
Pep Guardiola's team are rushing to get Zlatan Ibrahimovic and Lionel Messi back to fitness for the potentially decisive encounter.
Argentina forward Messi picked up a thigh muscle injury in Saturday's 1-1 La Liga draw at Athletic Bilbao and Ibrahimovic missed the game, also dogged by a thigh problem.
Defender Eric Abidal and midfielder Yaya Toure have been struck by the H1N1 virus but Guardiola refused to ring the alarm bells over his mounting problems.
"If players aren't there... we'll play with others. You don't win titles with two or three players," he said after the Bilbao game.
Inter will have Eto'o back in the starting line-up after the Cameroon international was a substitute in Saturday's 3-1 win at Bologna.
Ex-Real Madrid playmaker Wesley Sneijder, who scored the late winner in their 2-1 comeback win at Dynamo Kiev, may return after missing the Bologna victory with a knock.
Former Barca midfielder Thiago Motta could also feature having impressed for Inter of late after coming back from niggling injuries.
"Eto'o will be a starter in Barcelona," Inter coach Jose Mourinho told reporters, with red-hot Diego Milito set to partner Eto'o up front.
"The most important thing will be our minds, not the tactics or technique. Going there and playing to test our personality is the most important aspect."
Mourinho was also convinced former Inter frontman Ibrahimovic would return for the game: "He is 99.9999% sure to play."
Bayern Munich have yet to win a home game in Group A and, although they should have little trouble breaking their duck against Maccabi tomorrow, it may prove too late.
Third with four points from as many games, Bayern are four behind Juventus and will be eliminated if the Italians win away to a Girondins team who have nothing play for apart from their reputation.
With Bayern seventh in the Bundesliga, failure would heap further pressure on beleaguered coach Louis van Gaal.
Liverpool, who can ill afford to miss out on the lucrative final stages, are already without key striker Fernando Torres for tonight's trip to Hungary in Group E.
Rafael Benitez's team are third with four points, five behind Fiorentina who could already be out of touch when they visit Anfield on the final match day.
Failure to win will condemn Liverpool to an early exit as would a Fiorentina victory against Lyon.
Group C leaders Milan will qualify for the last 16 if they beat Olympique Marseille at home tomorrow.
A Milan win would also enable Real Madrid to go through provided they can beat Swiss champions FC Zurich, who have already shipped 12 goals in four games and lost 5-2 at home to the Spanish side earlier in the group.
Milan and Real - whose Bernabeu stadium will host the final - have seven points apiece, one ahead of Marseille.
A draw at home to Standard Liege would be enough for Group H leaders Arsenal to qualify.